Basic Virology I. Properties replication and classification of viruses 1. Size and shape Size range from 20-300 nm Shape : most of viruses are spherical or filamentous or complex or helical 2. Structure a. Genome : Viruses contain either DNA or RNA b. Capsid: a protein coat enclosing the genome and core protein c. Envelope : Lipid bilayer membrane surrounding the capsid of some viruses. 1 Virus replication: in host cells involves the following steps 1. Attachment to cell surface molecules (receptors) 2. Penetration of the viruses into the host cell by: - Endocytosis - Injection of nucleic acid - Fusion of envelope with host membrane 3. Replication of viral protein of nucleic acid and attached core protein in order to direct the host cell ribosome to produce viral proteins. 4. Assembly and maturation to form viral particles (virions, empty particles). 5. Release of the virus. 2 3 Bacteriophages Definition: Viruses that infect bacteriophages. 4 bacteria are known as Virus classification: Viruses can be classified according to: 1. Disease or organ system involved 2. Nucleic acid type/virus structure 3. Replication. Detection of virus infections 1. Direct detection of virus particles, viral antigen, viral lesions or nucleic acid, by microscope, particle agglutination, immunoflouresence, serology, PCR or RT-PCR. 2. Indirect detection of virus-specific host response by serology e.g. complement fixation test , haemagglutionation test , ELISA, etc. 5 Common viral infection 6 I. RNA viruses 1. Influenza virus Common cause of Respiratory tract infection Three types A, B and C Spread by droplets Infection of upper respiratory tract causing; incubation period 1-4 days followed by virus replication upper in upper respiratory tract. Epidemic occurs in types A, B, C but pandemic occurs mostly in type A. Treatment : Amantadine or rimantadine , for prophylaxis only. Prevention: inactivated vaccine (whole virus or subunit given intramuscularly) have an efficacy of 60-80% . 7 8 2. Mumps Transmission: By droplet or contact with saliva. Occur in children 5-15 y/o Incubation period is 18-21 days. There is a short prodromal phase (48 hr) of malaise and fever followed by parotid gland enlargement. Complication: - Meningitis, often mild in < 5% of cases - Epididymo-orchitis in about 25% of adult males infected with the virus. - Pancreatitis, myocarditis, arthritis, oophoritis. Prevention: Attenuated live virus vaccine is normally given in combination with measles and rubella vaccine (MMR) in childhood immunization schemes. 9 10 3. Measles: Transmission by Droplet spread. Highly infectious. Incubation period is 9-10 days. There is a prodromal phase (48 h) of fever, cough , rhinitis and conjunctivitis, followed by the appearance of a maculopapular rash starting on the face and trunk, and spreading peripherally; lesion also present on the mucosa , particularly in the mouth. Complication: - Pneumonia - Encephalitis - Otitis media Prevention: Attenuated live virus vaccine is normally given in combination with rubella and mumps vaccine (MMR). 11 4. Rubella Transmission by Droplets Incubation period is 14 days, with primary replication in the cervical lymph nodes , followed by rash Primary infection during the first 12 weeks of pregnancy often causes generalized fetal infection leading to intrauterine death /abortion , nerve deafness, cardiac abnormalities, hepatosplenomegaly , jaundice (congenital rubella syndrome). Enlargement of the suboccipital lymph node is a typical feature. Prevention: MMR vaccine 12 5. Polio viruses Cause poliomyelitis which affect C.N.S. Only a minority of polio infection is paralytic. Infection occurs by: - Oral route through contaminated food, milk or water, - Stools of a cases or a carrier. - House flies play a mechanical role in transmission. - Respiratory transmission After polio virus infection, one of the following pictures may occur 1. In-apparent infection: in which primary replication of the virus occurs in the oropharynx and intestinal mucosa the virus excreted in the stool or pharyngeal mucus 2. Abortive poliomyelitis: virus will go to lymph nodes with subsequent blood invasion may occur. This is accompanied with fever , malaise and gasterointestinal manifestation. 3. Paralytic poliomyelitis: when virus reach CNS via blood stream leading to meningitis and paralysis. Meningitis may occur without paralysis. 13 Most of infection occur as in-apparent or abortive. Paralytic poliomyelitis occur in 0.1-1% of cases only. Vaccination: Sabin ' living attenuated vaccine Living non paralytic strain Active immunization of all infants starting when 3 months old. Giving orally : 3 doses are required to ensure multiplication in gut with both local (IgA in gut) and serum antibody production. 6. Rota viruses Responsible for 50-60% of acute gastroenteritis in infants and children between age 6 months- 12 years. Infect cells in the villi of the small intestine disturb transport mechanisms; impairing sodium and glucose absorption. The damaged cell slough in the lumen of the intestine leading to release of large quantities of the virus which appears in the stools. Diagnosis based on the demonstration of the virus or its antigen in the stool of the patient using ELISA /Agglutination test. 14 7. Human immunodeficiency virus (HIV) Two types HIV-1 & HIV-2 Replication: - Attachment to T lymphocyte (CD4 cells) - Penetration by endocytosis - Replicatoin - Assembly : intracytoplasmic mophogenesis - Synthesis of DNA by viral reverse transcriptase - Release of virus particles by budding Diagnosis: by detection of HIV-specific antibody by passive particle agglutination test, ELISA, Western blotting or PCR Transmission by infected blood, sexual intercourse or from mother to child during pregnancy early impairment of immune cells specially T cells (CD4) humoral antibody response against HIV specific protein develps in later stage deficiency of both the humoral and cellular immune response develops. Disease: Acquired immunodeficiency syndrome (AIDS) characterized by severe disease due to generalized infections with bacteria, virus, fungi , protozoa and associated with tumors (Kapposi’s sarcoma, lymphoma) 15 Treatment: Zidovudine (azidothymidine) limited response. Other anti HIV compounds (dideoxycytidine). 16 6. Hepatitis A virus (HAV) Transmitted by fecal-oral route. Outbreaks have been associated with infected food handlers and ingestion of contaminated shellfish. Clinically: - Incubation period 2-6 weeks followed by malaise, anorexia, nausea and right upper quadrant pain. - Jaundice appear during the second week and normally last several weeks, but may be prolonged. - Fulminant liver failure occur in rare case. Chronic liver disease is not a feature of HAV infection. Disease: Acute hepatitis. In most cases there is complete recovery, with specific antibody response persisting lifelong. There is not carrier state Diagnosis: - Liver function tests show markedly elevated serum levels of liver enzymes (aminotransferases) and bilirubin. - Diagnosis is confirmed by the detection of serum IgM antibody to HAV. Treatment: General bed rest. Vaccine now available. 17 7. Hepatitis C virus (HCV). HCV is the cause of about 90% of hepatitis. Transmission occur in infected blood product, intravenous drug abuse, ? sexual transmission) Clinical features: incubation 2-6 months. The hepatitis is often mild but frequently progresses to chronic active hepatitis and cirrhosis after many years (> 25 years), with an increased risk of developing liver carcinoma. Diagnosis: by serology test, antibody to HCV and polymerase chain reaction (HCV-PCR). Prevention: no vaccine available yet. 18 II. DNA viruses 1. Herpes simplex virus (HSV) There are two serotypes, HSV 1 & HSV 2. Transmission is via virus infected saliva (HSV 1), sexual contact (HSV 2) or direct contact with vesicles. Following primary infection (often asymptomatic), HSV remains latent in the sensory ganglia, reactivation results in secondary infection. Clinical features: - Stomatitis: seen in children and immunocompramized patients. - Herpes labialis (cold sore): crops of vesicles around lips; result from reactivation of HSV in response to various stimuli (e.g. stress, sunlight). - Central nervous system infection: meningitis , encephalitis - Genital infection - Eye infection - Multisystem infection in the immunocompromized. Treatment: Acyclovir is useful for active infection, but does not eliminate latent HSV. 19 20 2. Hepatitis viruses : Hepatitis B Virus (HBV) Major cause of parenterally transmitted hepatitis. Virus : DNA virus , consisting of - Core , DNA circular genome - Nucleocapsid (hepatitis B core antigen , HBcAg) - Envelope (Hepatitis B surface , HBsAg) - (HBeAg) is a cleavage produce of the core found on infected cells or free in serum. Transmission: is by percutaneous and permucosal route, there are three important mechanism of transmission; - Contact transmission via bodily secretion (e.g. blood, semen and vaginal fluid) - Maternal infant transmission across the placenta or during delivary. - Percutaneous transmission: e.g. parenteral drug abuse and health care workers involved needlestick injuries. Infection via transfusion of contaminated blood product. Chronic HBsAg carriers have an increased risk in developing hapatocellular carcinoma. 21 Clinically : an incubation period 6 weeks to 6 months is followed by malaise, anorexia and jaundice. Disease: acute and chronic hepatitis ; hepatocellular carcinoma. Diagnosis: serological tests are made by immunoassay detecting HBsAg, HBeAg, and antibodies to HBcAg (IgM, IgG), anti-HBeAg, anti-HBsAg. Treatment: corticosteroids and azathioprine are used in severe cases of chronic but not acute hepatitis. Interferon is given in cases of chronic active hepatitis. Prevention: HBV vaccine. Neonatal vaccination prevent transmission from carrier mother. 22 3. Cytomegalovirus (CMV) caused by human cytomegalovirus (HCMV) dsDNA virus causes formation of intranuclear inclusion bodies and cytoplasmic inclusions virus shed in semen and cervical solutions can also be transmitted by blood transfusions and organ transplants usually asymptomatic infection with viremia. Infection of the neonate may be azquired in utero. 10% of infected infants are symptomatic at birth, showing lethargy, jaundice, convulsions, thrombocytopenia, hepatosplenomegaly. 60% of infants born to infected mothers acquire the disease by breast milk during perinatal period. > 90% of surviving infected infants develop complications later in life that include mental retardation, hearing loss and learning disabilities. can be serious in immunocompromised individuals symptoms often resemble mononucleosis treatment, prevention, and control antiviral agents (Gancyclovir) used for high-risk patients avoiding close personal contact with actively infected individual 23